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OBJECTIVES: We investigated the reversibility of tenofovir disoproxil fumarate (TDF)-associated renal decline and tubular dysfunction using different antiretroviral strategies. METHODS: A successive evaluation of renal [estimated glomerular filtration rate (eGFR)] and tubular (phosphataemia, proteinuria, albuminuria, phosphaturia, uricosuria, glycosuria and tubular proteinuria) parameters was performed in 231 patients, before and after switching from TDF to abacavir (n = 60), using dual therapy (n = 49), or continuing the same regimen including TDF (n = 122). RESULTS: In a successive evaluation after a median of 8.86 months, or less time if treatment was switched (4.8 months vs. 13.3 months to second evaluation; P < 0.01), a significant improvement in eGFR (median change +0.3 vs. -2.91 mL/min/1.73 m2 in patients who did not discontinue TDF; P = 0.04) and tubular dysfunction (median change -40% vs. +30%, respectively; P < 0.01) was observed. Lineal regression showed that age (ß = -0.14; P = 0.04), previous eGFR decline (ß = -0.42; P < 0.01), and time on TDF (ß = -0.19; P = 0.04) were associated with impaired eGFR recovery. There were no differences in eGFR slopes between patients using abacavir instead of TDF and those using a dual therapy, who showed similar improvement in proteinuria (-22% vs. -19%, respectively), phosphaturia (+10.1% vs. +9.4%, respectively), and urinary beta-2-microglobulin (-9% vs. -15%, respectively; P > 0.1 for all), although patients receiving the dual regimen were more heavily pretreated. A eGFR decrease (-6.17 mL/min/1.73 m2 ) was observed in patients taking dolutegravir or rilpivirine, but with similar improvement to that observed in the rest of switching patients in tubular abnormalities. CONCLUSIONS: Tenofovir disoproxil fumarate discontinuation was associated with a rapid and significant improvement in eGFR and tubular abnormalities, regardless of whether abacavir or dual therapy was chosen. Switching to a regimen that included dolutegravir and/or rilpivirine was associated with a eGFR decrease without differences in the rate of tubular dysfunction improvement in comparison with the rest of patients who discontinued tenofovir.
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A robust and simple sensing scheme utilizing a Mid-Infrared Light Emitting Diode (MIR-LED) and based on Differential Mode Excitation Photoacoustic (DME-PA) spectroscopy is presented. A MIR-LED light source in combination with optical correlation is used for simplicity and compactness. The sensing setup takes advantage of the non-linearity in the excitation of various acoustic modes in a cylindrical resonant photoacoustic cell to provide a high selectivity. The sensing device is tested using methane and hydrocarbon mixtures (propane, butane). The obtained limit of detection for methane is 25 ppm m-1. Using the presented DME-PA scheme, the derived gas concentration is hardly affected neither by intensity fluctuations of the light source nor by any microphone or electronics drifts. Furthermore, a considerably improved selectivity is obtained compared to conventional Non-Dispersive Infrared (NDIR) techniques.
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OBJECTIVE: Interest in oral exfoliative cytology has increased with the availability of molecular markers that may lead to the earlier diagnosis of oral squamous cell carcinoma. This research aims to compare the efficacy of three different instruments (Cytobrush, curette and Oral CDx brush) in providing adequate material for molecular analysis. METHODS: One hundred and four cytological samples obtained from volunteer healthy subjects were analysed using all three instruments. The clinical and demographical variables under study were age, sex and smoking habits. The three instruments were compared for their ability to obtain adequate samples and for the amount of RNA obtained using quantitative real-time polymerase chain reaction (PCR-qRT) analysis of the Abelson (ABL) housekeeping gene. RESULTS: RNA of the ABL gene has been quantified by number of copies. Adequate samples were more likely to be obtained with a curette (90.6%) or Oral CDx (80.0%) than a Cytobrush (48.6%); P < 0.001. Similarly, the RNA quantification was 17.64 ± 21.10 with a curette, 16.04 ± 15.81 with Oral CDx and 6.82 ± 6.71 with a Cytobrush. There were statistically significant differences between the Cytobrush and curette (P = 0.008) and between the Cytobrush and OralCDx (P = 0.034). There was no difference according to the demographical variables. CONCLUSIONS: Oral exfoliative cytology is a simple, non-invasive technique that provides sufficient RNA to perform studies on gene expression. Although material was obtained with all three instruments, adequate samples were more likely to be obtained with the curette or Oral CDx than with a Cytobrush. The Oral CDx is a less aggressive instrument than the curette, so could be a useful tool in a clinical setting.
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Carcinoma de Células Escamosas/diagnóstico , Técnicas Citológicas/instrumentación , Detección Precoz del Cáncer/instrumentación , Mucosa Bucal/citología , ARN/aislamiento & purificación , Adulto , Carcinoma de Células Escamosas/genética , Técnicas Citológicas/métodos , Detección Precoz del Cáncer/métodos , Femenino , Dosificación de Gen , Genes abl , Marcadores Genéticos , Humanos , Masculino , ARN/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Análisis de Secuencia de ARN , Fumar/efectos adversos , Adulto JovenRESUMEN
OBJECTIVES: To highlight the most characteristic histopathological findings of oral lichen planus and their correlation with the clinical manifestations and forms. STUDY DESIGN: We performed a retrospective study of 50 biopsied and diagnosed cases of oral lichen planus obtained over a period of 11 years, spanning from May 1998 to April 2009. We analyzed the age and sex of the patient, type of lichen planus, location and different histopathological findings, comparing them with the clinical lesions. RESULTS: Seventy eight percent of the patients are female and 22% are male, with an average age of 56.06 years for both sexes. The most frequent clinical form is reticular, present in 78% of the cases, and the most common location is the buccal mucosa, present in 70% of the patients. Hydropic degeneration of the basal layer and lymphocytic infiltration in the subepithelial layer are observed in the entire sample. Signs of atypia were identified in 4% of the cases, but without dysplasic features. Other common histological findings were the presence of necrotic keratinocytes (92%), hyperplasia (54%), hyperkeratosis (66%), acanthosis (48%), and less frequently, serrated ridges (30%) and the presence plasma cells (26%). CONCLUSIONS: Oral lichen planus is a disease that is more common in women, usually appearing in the fifth and sixth decades of life. The most common clinical form is reticular, manifesting mainly in the buccal mucosa. Histological findings characteristic of oral lichen planus include hydropic degeneration of the basal layer, lymphocytic infiltration in the subepithelial layer and the absence of epithelial dysplasia; however, it is also frequent to observe hyperplasia phenomena at the epithelial level, hyperkeratosis, acanthosis and the presence of necrotic keratinocytes.
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Liquen Plano Oral/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Liquen Plano Oral/diagnóstico , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Collagen hydrogels are among âthe most well-studied platforms for drug delivery and in situ tissue engineering, thanks to their low cost, low immunogenicity, versatility, biocompatibility, and similarity to the natural extracellular matrix (ECM). Despite collagen being largely responsible for the tensile properties of native connective tissues, collagen hydrogels have relatively low mechanical properties in the absence of covalent cross-linking. This is particularly problematic when attempting to regenerate stiffer and stronger native tissues such as bone. Furthermore, in contrast to hydrogels based on ECM proteins such as fibronectin, collagen hydrogels do not have any growth factor (GF)-specific binding sites and often cannot sequester physiological (small) amounts of the protein. GF binding and in situ presentation are properties that can aid significantly in the tissue regeneration process by dictating cell fate without causing adverse effects such as malignant tumorigenic tissue growth. To alleviate these issues, researchers have developed several strategies to increase the mechanical properties of collagen hydrogels using physical or chemical modifications. This can expand the applicability of collagen hydrogels to tissues subject to a continuous load. GF delivery has also been explored, mathematically and experimentally, through the development of direct loading, chemical cross-linking, electrostatic interaction, and other carrier systems. This comprehensive article explores the ways in which these parameters, mechanical properties and GF delivery, have been optimized in collagen hydrogel systems âand examines their in vitro or in vivo biological effect. This article can, therefore, be a useful tool to streamline future studies in the field, by pointing researchers into the appropriate direction according to their collagen hydrogel design requirements.
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Peripheral ossifying fibromas are benign mesenchymal lesions that usually arise in the anterior maxilla of young female patients. Histologically they consist of spindle cell proliferation with focal mineralisation. We reviewed 48 specimens from 41 patients and recorded the clinical data, sex, and age of the patients, site and size of the lesions, treatment, and postoperative outcome. Histologically the presence of mature, woven bone, cementum, and calcifications were evaluated and evaluated immunohistochemically. Lesions were more frequent in female patients in the third and fourth decade, and were usually in the lower maxilla and smaller than 2cm. All lesions were conservatively excised, and they relapsed in eight patients. Histopathologically, the lesions were poorly circumscribed, moderately cellular proliferations, with no discernible architectural pattern. All tumours showed some degree of mineralisation, the presence of immature bone being the most common. Immunohistochemical examination showed staining of tumoural cells for smooth muscle actin and CD68. Lesions tended to occur more commonly in female patients, but one decade later than usually reported. We found a higher recurrence rate in lesions that contained cementum-like material but without bone formation, suggesting a lack of maturation in this group. Immunohistochemical results were consistent with myofibroblastic differentiation but they added no information about the behaviour of the lesions.
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Calcinosis , Fibroma Osificante , Neoplasias Gingivales , Calcificación Fisiológica , Calcinosis/patología , Femenino , Fibroma Osificante/patología , Neoplasias Gingivales/patología , Humanos , MaxilarAsunto(s)
Antígenos de Neoplasias/genética , Moléculas de Adhesión Celular/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Eliminación de Secuencia , Adulto , Anciano , Anciano de 80 o más Años , Reparación de la Incompatibilidad de ADN/genética , Molécula de Adhesión Celular Epitelial , Exones , Femenino , Pruebas Genéticas , Humanos , Masculino , Persona de Mediana Edad , Tasa de Mutación , Factores de RiesgoRESUMEN
Sirolimus is a powerful immunosuppressive drug initially used in kidney transplant patients but now increasingly employed in recipients of other types of solid organ transplants, such as liver, heart, lung, or pancreas. Sirolimus is indicated for rescue therapy and to reduce the toxic side effects of calcineurin inhibitors. However, its use has been associated with an uncommon but important pulmonary toxicity. Reports have described interstitial pneumonitis, bronchiolitis obliterans, organizing pneumonia, and alveolar proteinosis. We present the case of a liver transplant patient with interstitial pneumonitis associated with sirolimus.
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Inmunosupresores/efectos adversos , Trasplante de Hígado/inmunología , Enfermedades Pulmonares Intersticiales/inducido químicamente , Sirolimus/efectos adversos , Humanos , Cirrosis Hepática Alcohólica/cirugía , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Combinación Trimetoprim y Sulfametoxazol/uso terapéuticoRESUMEN
A robust and simple gas sensor based on a novel photoacoustic scheme named "differential mode excitation photoacoustic spectroscopy (DME-PAS)" is presented. This method takes advantage of the selective excitation of two different modes in a resonant photoacoustic cell. A blackbody light source is used for simplicity in combination with optical correlation to provide a good selectivity. The frequency response of the proposed resonant cell is modeled using the extended Helmholtz resonator theory. The DME-PAS device is tested using acetone vapor and a model developed to describe its response when the gas concentration is varied. The obtained limit of detection is 25 ppm m(-1) for acetone in room air. Using DME-PAS, the derived gas concentration is affected neither by intensity fluctuations of the light source nor by any microphone drifts.
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Acústica/instrumentación , Gases/análisis , Fotometría/instrumentación , Análisis Espectral/instrumentación , Diseño de Equipo , Análisis de Falla de Equipo , Fotometría/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Análisis Espectral/métodosRESUMEN
INTRODUCTION: The clinical diagnosis aims to identify the degree of affectation of the psycho-physical state of the patient as a guide to therapeutic intervention. In stress, the lack of a measurement tool based on a reference makes it difficult to quantitatively assess this degree of affectation. AIM: To define and perform a primary assessment of a standard reference in order to measure acute emotional stress from the markers identified as indicators of the degree. SUBJECTS AND METHODS: Psychometric tests and biochemical variables are, in general, the most accepted stress measurements by the scientific community. Each one of them probably responds to different and complementary processes related to the reaction to a stress stimulus. The reference that is proposed is a weighted mean of these indicators by assigning them relative weights in accordance with a principal components analysis. RESULTS: An experimental study was conducted on 40 healthy young people subjected to the psychosocial stress stimulus of the Trier Social Stress Test in order to perform a primary assessment and consistency check of the proposed reference. The proposed scale clearly differentiates between the induced relax and stress states. CONCLUSIONS: Accepting the subjectivity of the definition and the lack of a subsequent validation with new experimental data, the proposed standard differentiates between a relax state and an emotional stress state triggered by a moderate stress stimulus, as it is the Trier Social Stress Test. The scale is robust. Although the variations in the percentage composition slightly affect the score, but they do not affect the valid differentiation between states.
TITLE: Aproximacion a una escala de referencia de estres emocional agudo.Introduccion. El diagnostico clinico persigue identificar el grado de afectacion del estado psicofisico del paciente como orientacion hacia la intervencion terapeutica. En el estres, la falta de un instrumento de medicion por comparacion con una referencia dificulta la valoracion cuantitativa del nivel de afectacion. Objetivo. Definir y hacer una primera validacion de un patron de referencia para la medida del estres emocional agudo a partir de marcadores identificados como indicadores del nivel. Sujetos y metodos. En general, las medidas mas solidas y aceptadas de estres por la comunidad cientifica son los test psicometricos y las variables bioquimicas. Cada uno de ellos responde probablemente a procesos distintos y complementarios de la reaccion frente a un estimulo estresante. La referencia que se propone es una media ponderada de estos indicadores, asignandoles pesos relativos de acuerdo con un analisis de componentes principales. Resultados. Para una primera aproximacion y verificacion de coherencia de la referencia propuesta, se ha utilizado un estudio experimental con una muestra de 40 jovenes sanos sometidos al estimulo estresante psicosocial del Trier Social Stress Test. La escala propuesta diferencia netamente entre los dos estados con distintos niveles de estres inducido. Conclusiones. Aceptando la subjetividad de la definicion, y a falta de una validacion posterior con nuevos datos experimentales, el patron propuesto diferencia entre un estado de relax y uno de estres emocional generados con un estimulo estresante moderado, como es el Trier Social Stress Test. La escala es robusta, ya que variaciones en la composicion porcentual repercuten ligeramente en la puntuacion, pero no en la diferenciacion valida entre estados.
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Índice de Severidad de la Enfermedad , Estrés Psicológico/diagnóstico , Biomarcadores , Electrodiagnóstico , Femenino , Glicopéptidos/sangre , Humanos , Hidrocortisona/sangre , Masculino , Análisis de Componente Principal , Prolactina/sangre , Pruebas Psicológicas , Psicometría , Estándares de Referencia , Relajación , Estrés Psicológico/sangre , Estrés Psicológico/fisiopatología , Estrés Psicológico/psicologíaRESUMEN
During the last 12 years, an increasing frequency in condemnation of hunted red deer and wild boar carcasses due to the presence of tubercle-like lesions has been observed in Extremadura (Western Spain). Before 1993, tuberculosis was a very rare finding in hunted animals. The current tuberculosis regional prevalence in cattle approaches 0.4% after years of expensive test and slaughter campaigns. It is imperative to investigate the epidemiology of Mycobacterium bovis infection in red deer and wild boar in order to keep a good health status and to maintain the effectiveness of domestic species TB eradication programs. The present paper evaluates the problem in Sierra de San Pedro, estimating the prevalence of TB in wild boar and red deer, the main wild artiodactyls in the area, and domestic cattle since 1992-2004, by the use of a low-cost surveillance method based on detailed pathological inspection of hunted animal carcasses. Microbiology and molecular epidemiology studies on several M. bovis isolates from domestic and wild animals helped to define the interspecies contacts. These findings, as well as recent history of game estates management and descriptive epidemiology field work, throw light on the rise and maintenance of these epizootics.
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Ciervos , Mycobacterium bovis/aislamiento & purificación , Sus scrofa , Enfermedades de los Porcinos/epidemiología , Tuberculosis Bovina/epidemiología , Tuberculosis/veterinaria , Animales , Animales Domésticos , Animales Salvajes , Bovinos , Brotes de Enfermedades/veterinaria , Ecosistema , Prevalencia , Estudios Retrospectivos , España/epidemiología , Tuberculosis/epidemiología , Tuberculosis/prevención & control , Tuberculosis Bovina/prevención & controlRESUMEN
AIM: To analyze the efficacy and safety of mycophenolate mofetil (MMF) as monotherapy in liver transplant patients who have adverse effects associated with calcineurin inhibitors (CNIs). PATIENTS AND METHODS: Seventeen patients, 13 men and four women, mean age 62 years, who received a liver transplant between 1998 and 2003 and initial immunosuppressive therapy with CNIs (10 tacrolimus and seven cyclosporine), were converted to monotherapy with MMF due to adverse events associated with CNIs: chronic renal failure in 16 patients (four with diabetes mellitus and seven with hypertension) and neurotoxicity in one patient. The mean time between transplant and starting monotherapy was 32 months (range: 18 to 70) and the mean follow-up time on monotherapy was 20 months (range: 8 to 39). MMF was introduced gradually at the same time as the CNIs were reduced. RESULTS: There was a progressive decrease in creatinine during the initial months. Compared with baseline levels, the differences at 3 and 6 months of monotherapy were significant (P < .001), remaining so throughout the follow-up period. Renal function improved in 15 of 17 patients (88%) and normalized in 10 of 17 (60%). The patient with neurotoxicity due to CNI improved. One patient (6%) had moderate rejection that was corrected after reintroducing tacrolimus. In two patients it was necessary to suspend MMF, one due to gastrointestinal intolerance and the other due to severe myelotoxicity and Pneumocystis jiroveci infection. Other, minor adverse events were corrected by adjusting the dose: one herpes zoster, two diarrhea, and two anemia. CONCLUSIONS: Monotherapy with MMF efficiently and safely corrected renal dysfunction associated with CNIs, with few side effects and a low incidence of rejection.
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Trasplante de Hígado/fisiología , Ácido Micofenólico/análogos & derivados , Creatinina/sangre , Estudios de Seguimiento , Humanos , Inmunosupresores/uso terapéutico , Pruebas de Función Renal , Trasplante de Hígado/inmunología , Masculino , Persona de Mediana Edad , Ácido Micofenólico/uso terapéutico , Estudios Retrospectivos , Seguridad , Factores de TiempoRESUMEN
Although estrogen receptor (ER)-alpha is expressed in both benign and malignant ovarian tumors, the role of ER in ovarian carcinogenesis of epithelial tumors is still unknown. In view of the recent characterization of ER-beta, a second form of ER that seems to be highly expressed in ovaries, we reexamined this issue by studying the relative expression of ER-alpha and -beta in human ovarian tumor progression. We developed a competitive PCR assay based on coamplification of the two ERs in target nucleotide sequences displaying a high homology (exons 3 and 4). Coamplification experiments with varying amounts of plasmids containing ER-alpha and -beta cDNAs showed that this assay was reliable for discriminating as little as a 2-fold difference in the initial ER-alpha:ER-beta cDNA ratio. The relative expression of ER-alpha compared with ER-beta mRNAs was studied in human ovarian cancer cell lines (n = 5) and in normal ovaries (n = 6), then in human benign and malignant tumor samples including ovarian cysts (n = 24), borderline tumors (n = 3), and cancers (n = 10). In normal ovaries, ER-beta mRNA was the predominant ER form, whereas in ovarian cancer cell lines ER-alpha mRNA was markedly increased as compared with ER-beta. In benign and borderline tumors, ER-beta mRNA was detected in 78% of tumors, whereas ER-alpha mRNA was detected in 29%. In ovarian carcinomas, both ER-alpha and -beta mRNAs were expressed in 80% of tumors. The ER-alpha:ER-beta mRNA ratio was >1 in only one cyst sample (4%). In contrast, the ER-alpha:ER-beta mRNA ratio was markedly increased in ovarian cancers because 60% showed an ER-alpha:ER-beta mRNA >1. In situ hybridization experiments showed overlapping tissular distribution of ER-beta and -alpha expression in cancers and cysts, with a main localization in the epithelium and only a low level of expression in stromal cells. In summary, we found an increase in the ER-alpha:ER-beta mRNA ratio in ovarian carcinomas as compared with normal ovaries and cysts. These data suggest that overexpression of ER-alpha relative to ER-beta mRNA may be a marker of ovarian carcinogenesis.
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Biomarcadores de Tumor/biosíntesis , Neoplasias Ováricas/metabolismo , ARN Mensajero/biosíntesis , Receptores de Estrógenos/biosíntesis , ADN Complementario/genética , ADN Complementario/metabolismo , Progresión de la Enfermedad , Receptor alfa de Estrógeno , Receptor beta de Estrógeno , Femenino , Humanos , Hibridación in Situ , Enfermedades del Ovario/metabolismo , Enfermedades del Ovario/patología , Neoplasias Ováricas/patología , Neoplasias Ováricas/ultraestructura , Plásmidos , Isoformas de Proteínas , Receptores de Estrógenos/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales CultivadasRESUMEN
BACKGROUND: Simple, reliable measures of the quality of the environment in which a child was reared that can be used in clinical research and practice are lacking. METHOD: The reliability and validity of a global scale to retrospectively appraise the quality of that environment were examined. Fifty-three clinicians from 4 centers in Australia and 1 in Hong Kong, People's Republic of China, used the scale to rate 7 case vignettes; 4 clinicians rated 20 medical records, and 49 rated 211 subjects after clinical interviews. RESULTS: Interrater reliability (intraclass correlation coefficient) was 0.82 (time 1) and 0.84 (time 2) for case vignettes, 0.90 for medical records, and 0.89 for clinical interviews. Consistency in time was high (r = 0.91). Lower ratings, indicative of a less adequate environment, were associated with a clinical diagnosis of oppositional defiant or conduct disorder. CONCLUSIONS: Our simple-to-use scale appears to measure reliably a relevant clinical construct and fills a gap among the instruments available. Ratings may be useful as a cost-effective index to consider in outcome studies, when examining response to treatment, or in other clinical research.
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Trastornos de la Conducta Infantil/diagnóstico , Composición Familiar , Estilo de Vida , Escalas de Valoración Psiquiátrica/estadística & datos numéricos , Medio Social , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/clasificación , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Australia , Niño , Trastornos de la Conducta Infantil/clasificación , Preescolar , China , Comparación Transcultural , Femenino , Hong Kong , Humanos , Masculino , Registros Médicos , Psicometría , Calidad de Vida , Reproducibilidad de los ResultadosRESUMEN
We compared the effect of estradiol on activator protein-1 (AP-1) activity in estrogen receptor positive (ER alpha+) and estrogen receptor negative (ER alpha-) human breast cancer cell lines transiently transfected with the AP-1-responsive reporter plasmid AP-1-TK-CAT and an ER alpha expression vector. While estradiol increased AP-1 activity in the ER alpha+ cell lines MCF7, ZR75.1, and T47D, it decreased (MDA-MB231 and BT20 cells) or had no significant effect (MDA-MB435 cells) on AP-1-mediated transcription in ER alpha- cells. Estradiol also inhibited AP-1 activity in ER alpha-MDA-MB231 cells stably transfected with ER alpha and in which ER alpha levels are close to those found in MCF7. Use of ER alpha mutant expression vectors demonstrated that the DNA-binding domain of ER alpha was needed for stimulation or inhibition of AP-1 activity by estradiol but suggested that ER alpha binding to estrogen-responsive elements was not required for these effects. Changes in regulation paralleled quantitative and qualitative changes in protein binding to AP-1 sites, as demonstrated by gel shift assay: protein binding was greater and DNA/protein complexes migrated faster for ER alpha--than for ER alpha+ cells. In fact, by Northern blot, a high level of Fra-1 mRNA was found in BT20 and MDA-MB231 cells as compared with ER alpha+ cells, and MDA-MB435 cells showed an intermediary level of expression. The differential expression of Fra-1 in MCF7 and MDA-MB231 cells was confirmed at the protein level by supershift experiments. In addition, overexpression of Fra-1 in MCF7 cells decreased the positive effect of estradiol while inhibition of Fra-1 expression in MDA-MB231 cells, by transient transfection of the Fra-1 antisense expression vector, abolished the negative effect of the hormone. In conclusion, we demonstrated that ER alpha- breast cancer cell lines differ from ER+ cells by a high level of AP-1 DNA-binding activity due, at least in part, to high Fra-1 constitutive expression. High Fra-1 concentration is crucial for the negative regulation of AP-1 activity by estradiol and thus may take part in estradiol-induced inhibition of cell proliferation in ER alpha- breast cancer cells transfected with ER alpha expression construct.
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Neoplasias de la Mama/metabolismo , Estradiol/farmacología , Expresión Génica , Proteínas Proto-Oncogénicas c-fos/genética , Factor de Transcripción AP-1/metabolismo , Northern Blotting , Neoplasias de la Mama/química , ADN/metabolismo , Genes fos/genética , Humanos , Proteínas Proto-Oncogénicas c-fos/farmacología , ARN Mensajero/metabolismo , Receptores de Estrógenos/análisis , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Proteínas Recombinantes de Fusión , Factor de Transcripción AP-1/genética , Transfección , Células Tumorales CultivadasRESUMEN
OBJECTIVE: Oppositional defiant disorder is a common clinical diagnosis that has attracted little research interest, and doubts about its validity as a distinct category remain. However, it underwent substantial changes from DSM-III to DSM-III-R, and more are proposed for DSM-IV. The objective of this study was to review the literature on this condition to establish its place in the psychiatric nosology. METHOD: The terms used in computerized searches of the literature included "oppositional disorder," "oppositional defiant disorder," and "oppositional behavior." Publications found by these searches were supplemented with references in articles, searches in the epidemiological literature, and noncomputerized searches. RESULTS: Findings of studies in which multivariate analyses were used support a distinction between oppositional defiant disorder and conduct disorder. In these studies, one-third of all community-based children with any psychiatric condition had a diagnosis of oppositional defiant disorder and used mental health services often. Symptoms of oppositional defiant disorder appear to be stable over time and to have a developmental profile and sex distribution different from those of conduct disorder. The reliability of the diagnosis is low. CONCLUSIONS: There is some support for oppositional defiant disorder as a category that reflects an oppositional-aggressive psychological dimension, which is different from a delinquent dimension. There is little evidence for making oppositional defiant disorder a part of the construct of conduct disorder and for making "lying" a criterion for it. Considerable impairment should be required for the diagnosis. A more detailed description of symptoms, including a threshold for considering them present, may increase reliability of the diagnosis.
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Trastornos de la Conducta Infantil/diagnóstico , Terminología como Asunto , Agresión/clasificación , Niño , Conducta Infantil/clasificación , Trastornos de la Conducta Infantil/clasificación , Preescolar , Decepción , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Estudios Prospectivos , Psicometría , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: Pharmacological treatments for certain psychiatric disorders in young people are often ineffective and may cause major side effects; thus, it is important to investigate other treatments. This article reviews the literature on the efficacy and safety of ECT in this age group and examines the evidence for the suggestion that it may be used inappropriately. METHOD: All studies published in English and other languages on the use of ECT in persons 18 years of age or younger were obtained. The reports were systematically reviewed and rated according to the quality of the information in several domains, yielding an overall quality score for each study. Individual cases from each report were then examined and grouped according to diagnosis and response to ECT. RESULTS: Sixty reports describing ECT in 396 patients were identified; most (63%) were single case reports. The overall quality was poor but improved in the more recent studies. There were no controlled trials. Rates of improvement across studies were 63% for depression, 80% for mania, 42% for schizophrenia, and 80% for catatonia. Serious complications were very rare, whereas minor, transient side effects appeared common. CONCLUSIONS: ECT in the young seems similar in effectiveness and side effects to ECT in adults. However, this conclusion is qualified by the lack of systematic evidence. More research and education of professionals and the public are needed. It is suggested that ECT registers be set up, that surveys and controlled trials be conducted, and that seizure thresholds, the optimal anesthetic, effects of concurrent medications, and cognitive consequences of ECT in the young be investigated.
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Terapia Electroconvulsiva/estadística & datos numéricos , Trastornos Mentales/terapia , Adolescente , Adulto , Factores de Edad , Trastorno Bipolar/terapia , Catatonia/terapia , Trastorno Depresivo/terapia , Terapia Electroconvulsiva/efectos adversos , Femenino , Humanos , Masculino , Esquizofrenia/terapia , Resultado del TratamientoRESUMEN
Clinicians have traditionally inquired about stressful life events preceding the onset of a psychiatric disorder. Axis IV of DSM-III attempted to improve on this by suggesting that a wide range of events be considered and that the information obtained be integrated into a global rating of severity. After reviewing recent evidence, the authors suggest that this process might result in ratings with lower reliability than expected. They also discuss some of the methodological difficulties in this field and explore directions for further research.
Asunto(s)
Acontecimientos que Cambian la Vida , Trastornos Mentales/diagnóstico , Humanos , Trastornos Mentales/clasificación , Trastornos Mentales/etiología , Escalas de Valoración Psiquiátrica , PsicometríaRESUMEN
OBJECTIVE: Personality disorders are a major mental health problem, but little information about their etiology and natural history is available. This study examined continuities between axis I disorders in adolescents and personality disorders in young adults. METHOD: The authors interviewed 145 young adults (mean age, 19.6 years) who had been diagnosed with a variety of DSM-III emotional and disruptive disorders during adolescence (mean age, 13.7 years). The Personality Disorder Examination was used to establish whether the subjects currently suffered from personality disorders. RESULTS: Subjects who had had disruptive disorders during adolescence showed high rates of all types of personality disorders (40% had a personality disorder at follow-up), while subjects who had had emotional disorders had a lower rate of personality disorders (12%). Men were more likely to have cluster A personality disorders, and women were more likely to have cluster C personality disorders. Disruptive diagnoses were associated with cluster B personality disorders, but emotional disorders did not show an association with cluster C personality disorders. Oppositional disorder did not increase the likelihood of passive-aggressive personality disorder. There was an association between attention deficit disorder with hyperactivity and borderline personality disorder. CONCLUSIONS: The rate of personality disorders was lower among young adults who had had emotional disorders during adolescence than among those who had had disruptive disorders, suggesting either that treatment for emotional disorders is more effective or that the personality psychopathology in these adolescents is not as severe as that in adolescents with disruptive disorders.
Asunto(s)
Trastornos Mentales/diagnóstico , Trastornos de la Personalidad/diagnóstico , Adolescente , Adulto , Factores de Edad , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Comorbilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Trastornos Mentales/epidemiología , Trastornos de la Personalidad/epidemiología , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Factores SexualesRESUMEN
The increasing number of factors to be taken into account in the oestrogen transcriptional process has created a need to develop a rapid screening method to evaluate their role in physiology and pathology. Molecular biology techniques enable gene expression studies at the mRNA level with small amounts of tissues. We therefore developed a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique using fluorescent oligonucleotides to analyse simultaneously a large panel of interrelated genes involved in the oestrogen transcriptional pathway using a moderately expressed housekeeping gene, the hypoxanthine phosphoribosyltransferase gene (HPRT), as the reference gene. Expression levels of oestrogen receptors (ERalpha, ERbeta), cofactors AIB1, RIP140, SMRT and the Fas-associated protein-tyrosine phophatase-1 (FAP-1) genes were evaluated in breast, endometrial and ovarian cancer cell lines and in three ERalpha-positive and three ERalpha-negative breast cancer tumours. This technique provides a rapid and reliable way to quantitate simultaneously numerous mRNAs of genes involved in the oestrogen pathway from small amounts of tissues.